World First Head Injury Research in Glasgow

July 21, 2011 10:44 AM

A single head injury may prompt dementia-like changes in the brain years after injury, a Glasgow study has revealed.

In a groundbreaking study appearing online in Brain Pathology, researchers from the Southern General Hospital in Glasgow, working with collaborators at the University of Pennsylvania, have identified widespread Alzheimer’s disease-like pathology in approximately one third of long-term survivors of a single head injury, even in young adults.

The researchers believe that this suggests Alzheimer’s disease-like neurodegeneration may be initiated or accelerated following a single head injury in a proportion of patients.

Over 150 thousand people in the UK suffer a head injury each year (also referred to as a traumatic brain injury (TBI)).

This new research provides us with the first clear evidence of abnormalities in the brains of survivors of a single head injury to support the growing clinical impression that, for many survivors, a head injury may develop into a chronic disease. In particular, TBI is an established risk factor for later development of dementia, including Alzheimer's disease.

Until this current work neurodegenerative pathology following a TBI had only been documented in a small number patients with a history of repetitive head injury, such as boxers or, more recently, American Footballers (termed chronic traumatic encephalopathy; CTE).

In this study, researchers compared post-mortem brains from 39 patients, surviving from 1-47 years after head injury, to uninjured, age-matched controls. Their results showed that the brains of TBI survivors contained a higher density and wider distribution of tau-positive neurofibrillary tangles and amyloid-beta plaques than the equivalent controls.

Specifically, years after a single injury, about a third of TBI cases showed tangle pathology similar in appearance to the tangles found in neurodegenerative diseases such as Alzheimer’s disease. Moreover, not only were high numbers of amyloid-beta plaques found years after TBI, but the majority of head injured cases displayed a particular form of plaque, neuritic plaques; again typical of those found in Alzheimer’s disease.

“These are exciting results", said the study's co-senior author Dr Willie Stewart, Consultant Neuropathologist at the Southern General Hospital in Glasgow and Honorary Clinical Senior Lecturer at the University of Glasgow. “What we have found, quite remarkably, is that a proportion of patients with a single head injury had widespread and large amounts of markers in their brains which are normally only seen in the very elderly or in patients with Alzheimer’s disease.

“This study may be significant in terms of understanding dementia. Dementia is a particular challenge, especially with an ageing population. In the vast majority of cases we do not currently know what triggers the process leading to dementia in the first place. However if we know when this process may begin, such as with a head injury, we can learn more about it and this could lead to new and more effective treatments.”

Dr Stewart recently received a grant from the American National Institutes of Health (NIH) to carry out research into the link between TBI and dementia. At the time the grant was considered as a coup for the service because the NIH, America’s medical research agency, rarely funds research outside the US.

Tau-positive neurofibrillary tangles and amyloid-beta plaques are both hallmarks of Alzheimer’s disease.

In the only previous work looking at tau after a single head injury, also from Glasgow, no similar pathology was found; though this was restricted to studies on patients dying less than four weeks after injury. Amyloid plaque pathology has been documented in patients dying acutely following head injury, but this acute plaque appears to resolve shortly after injury and differs from the Alzheimer’s-like plaques observed in this current study.
The present findings showing that two hallmark pathologies of Alzheimer’s disease can be found years after a single TBI. This may provide a pathological basis for the observation of an increased risk of dementia following TBI. Moreover, future research to better understand this long-term neurodegenerative process after a single head injury may reveal important targets for therapy development in dementia and TBI.

Co-senior author on this study: Douglas H. Smith, M.D., The Robert A. Groff Professor of Neurosurgery, Director of the Center for Brain Injury and Repair, University of Pennsylvania